title: Further analysis of the antinociceptive action caused by p-methoxyl-diphenyl diselenide in mice.
abstract: The objective of this study was to extend our previous findings by investigating in greater detail the mechanisms that might be involved in the antinociceptive action of p-methoxyl-diphenyl diselenide, (MeOPhSe)(2), in mice. The pretreatment with nitric oxide precursor, l-arginine (600 mg/kg, intraperitoneal, i.p.), reversed antinociception caused by (MeOPhSe)(2) (10 mg/kg, p.o.) or N(G)-nitro-l-arginine (l-NOARG, 75 mg/kg, i.p.) in the glutamate test. Ondansetron (0.5 mg/kg, i.p., a 5-HT(3) receptor antagonist) and SCH23390 (0.05 mg/kg, i.p.., a D(1) receptor antagonist) blocked the antinociceptive effect caused by (MeOPhSe)(2). Conversely, pindolol (1 mg/kg, i.p., a 5-HT(1A)/(1B) receptor/beta adrenoceptor antagonist), WAY 100635 (0.7 mg/kg, i.p., a selective 5-HT(1A) receptor antagonist), ketanserin (0.3 mg/kg, i.p., a selective 5-HT(2A) receptor antagonist), prazosin (0.15 mg/kg, i.p., an alpha(1)-adrenoreceptor antagonist), yohimbine (1.0 mg/kg, i.p., an alpha(2)-adrenoreceptor antagonist), sulpiride (5 mg/kg, i.p., a D(2) receptor antagonist), naloxone (1 mg/kg, i.p., a non-selective opioid receptor antagonist) and caffeine (3 mg/kg, i.p., a non-selective adenosine receptor antagonist) did not change the antinociceptive effect of (MeOPhSe)(2). (MeOPhSe)(2) significantly inhibited nociception induced by intraplantar (i.pl.) injection of bradykinin (10 nmol/paw) and Des-Arg(9)-bradykinin (10 nmol/paw, a B(1) receptor agonist). (MeOPhSe)(2) significantly inhibited phorbol myristate acetate (PMA, 0.03 mug/paw, a protein kinase C (PKC) activator)-induced licking response. These results indicate that (MeOPhSe)(2) produced antinociception in mice through mechanisms that involve an interaction with nitrergic system, 5-HT(3) and D(1) receptors. The antinociceptive effect is related to (MeOPhSe)(2) ability to interact with kinin B(1) and B(2) receptors and PKC pathway mediated mechanisms.
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil.
authors.forename: Cristiano R
authors.initials: CR
authors.lastname: Jesse
authors.forename: Joao B T
authors.initials: JB
authors.lastname: Rocha
authors.forename: Cristina W
authors.initials: CW
authors.lastname: Nogueira
authors.forename: Lucielli
authors.initials: L
authors.lastname: Savegnago
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D001555:Benzene Derivatives / Q000494:pharmacology*; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018698:Glutamic Acid / Q000633:toxicity; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D018377:Neurotransmitter Agents / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D016566:Organoselenium Compounds / Q000494:pharmacology*; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate
chemical_list: D000700:Analgesics; D001552:Benzazepines; D001555:Benzene Derivatives; D018492:Dopamine Antagonists; D004791:Enzyme Inhibitors; D018377:Neurotransmitter Agents; D016566:Organoselenium Compounds; D017981:Receptors, Neurotransmitter; C534628:SCH 23390; C528548:p-methoxy-diphenyl diselenide; C046722:bradykinin, des-Arg(1)-; D019335:Nitroarginine; D009569:Nitric Oxide; D018698:Glutamic Acid; D001120:Arginine; D019001:Nitric Oxide Synthase; D013755:Tetradecanoylphorbol Acetate; D001920:Bradykinin